H001 The intracellular deposition of energy from ionizing radiations initiates a cascade of molecular events which can express within that phase of the cell cycle through to later cell generations. Understanding these molecular events can lead to an understanding of the carcinogenic process and ultimately to circumvention or control. The microbeam is unique in that it can deliver a radiation insult to a known cell amongst others or subcellular compartments in many cells. Additionally precisely 1 particle [or more] can be delivered to a specific site, and it has been found that 1 alpha particle results in fewer cells progressing from G1 into S phase, thereby causing a cell cycle delay response. However more cells are delayed than show a p53 response while p21 expression can be found in non p53 responding cells. Clearly there is a fluence dependent increase in the percentage of cells responding, with however a strong indication that there is a non-random intra-nuclear sensitivity to alpha particle insult. The initiation of a stress response does not appear to be confined to nuclear perturbation, but can manifest following neighbor or cytoplasmic irradiation. This has implications for extrapolations in risk estimation.